We propose to characterize a new regulatory mechanism for normal human myeloid cell proliferation. The newly discovered stem cells (CFU-CMo) are stimulated by a factor from a human T-lymphocyte cell line (Mo) established from a patient with hairy cell leukemia. The stimulation of the CFU-CMo is greatly enhanced by a factor present in human serum and red blood cell lysate. Tests of bone marrow and blood cells from patients with chronic myelogenous leukemia indicate CFU-CMo are present in large numbers in the peripheral blood of these patients. We propose to physically isolate the stimulating factor from Mo-CM and the enhancing factor from human red blood cell lysate. Serum from Mo conditioned medium will be utilized as the source of the stimulating factor. Preliminary results suggest that the factors are glycoproteins in the 50,000 - 60,000 molecular weight range. They will be isolated using a combination of fractionation techniques. We will enrich the CFU-CMo population from normal human bone marrow using buoyant density gradient centrifugation, velocity sedimentation at 1 x g and fluorescence activated cell sorting. The enriched stem cell population and the purified factors will be used to elucidate the mechanisms of regulation including the relationship between CSF and CFU-CMo stimulating factor, the mode of action of the enhancing activity, and the relationship between CFU-C and CFU-CMo. We also propose to study this regulatory system in patients with myeloproliferative disorders. We will screen sera from patients for the presence of CFU-CMo stimulating factor and patient sera and red cell lysate for level of CFU-CMo enhancing factor. We will also measure the percentage of CFU-CMo in patient bone marrow and blood cells during different stages of diseases where expression is abnormal.